3. and metabolic regulation modify the expression of the dis-
order. Finally, it will examine the persistent metabolic
components of the disorder and the variable ovarian en-
docrine influences and environmental factors that may
playaroleinthemorbidityofthesyndromeinmenopause.
Taken together, the expression of PCOS may begin
early and the symptoms change across the lifespan. De-
termining the appearance and expression of the syndrome
at each stage of life will be important to expand the diag-
nosis and treatment of PCOS.
In Utero and Early Life
It is impossible to diagnose PCOS in infants and children
by symptoms, and genetic testing is not yet available to
determine which girls might be at risk. However, daugh-
tersofwomenwithPCOShavebeenstudiedininfancyand
childhood as proxies for children with PCOS based on the
strong heritability of PCOS in families (5, 6) and the pos-
sibility that in utero factors predispose to PCOS risk (1, 2).
Inthesestudies,anti-Mullerianhormone(AMH)levelsare
used to assess antral follicle count because levels are highly
correlated with antral follicle count on ultrasound and
reflect the number of small antral follicles in the ovary (7).
AMH levels also cluster with hyperandrogenism in prin-
ciple component analyses of PCOS, suggesting that AMH
levels can be used as a surrogate for ovarian hyperandro-
genism in women with PCOS (8). When AMH levels were
examined in daughters of women with PCOS, they were
increased in infancy, early childhood, and prepubertally
(9–11). The increased AMH levels were associated with
higher leptin levels in cord blood in infants and an in-
creased insulin response to glucose prepubertally com-
pared with controls (11). However, cord blood insulin
levels did not differ, and low-density lipoprotein (LDL)
and triglyceride levels were lower in these infants of
women with PCOS (12). Thus, it appears that girls at risk
for PCOS based on heritability have evidence for an in-
creased follicle complement and mild metabolic abnor-
malities compared with controls.
Based on data from animal models, it has been sug-
gested that an androgenic in utero environment is associ-
ated with PCOS-like features in exposed progeny. How-
ever, there are no data to support the model in humans.
Placental aromatase aromatizes maternal testosterone be-
fore fetal exposure, and there should be no androgen el-
evation in amniotic fluid. Subtle lower 3-hydroxysteroid
dehydrogenase 1 and aromatase activity has been de-
scribed in the placentas of women with PCOS (13). How-
ever, a large prospective study of maternal and umbilical
cord testosterone levels found no relationship with the
subsequent development of PCOS (14).
Other in utero factors may predispose to the develop-
mentofPCOS.Intrauterinefactorswithresultingeffecton
birth weight and possible changes in the intrauterine en-
vironment as a function of birth order are variables that
could play a role. Retrospective studies suggest that a sub-
set of girls born small for gestational age will later develop
early pubarche, early menarche, and PCOS (2, 15). Using
AMH as a proxy for increased follicle number, newborns
with low and high birth weights have higher AMH levels
than normal birth weight infants when measured at 2 to 3
Table 1. Phenotype of Women with PCOS Across the Lifespan and Similarities in Controls
PCOS Controls: Similarities to PCOS
Predisposing
factors
Genes, environment, in utero environment None
Infancy Increased AMH (proxy for follicle number) None
Childhood Increased AMH (proxy for follicle number) None
Puberty Premature pubarche (adrenarche), increased GnRH
pulse secretion, hyperandrogenism (exacerbated
by obesity), irregular menses (exacerbated by
obesity), increased ovarian volume/AMH, and
increased glucose-induced insulin response
Acne, irregular menses, and increased
ovarian volume
Reproductive
years
Hyperandrogenism (exacerbated by obesity),
irregular menses (exacerbated by obesity),
increased ovarian volume and follicle number;
over time, decreases in androgen levels, ovarian
volume, and follicle number; and menstrual
cycles may regularize
Decreases in androgen levels, ovarian
volume, and follicle number
Menopause Higher Ferriman-Gallwey score, prevalence of
hypertension, triglycerides, and cerebrovascular
morbidity
Weight, waist to hip ratio, systolic
blood pressure, prevalence of type
2 diabetes, fasting glucose, insulin,
HOMA, LDL, and cardiovascular
morbidity and mortality
2 Welt and Carmina Lifecycle of PCOS J Clin Endocrinol Metab
4. months of age (16). High birth weight infants have lower
adiponectin,suggestingdecreasedinsulinsensitivity.They
also demonstrate higher GnRH-stimulated FSH levels,
and both low and high birth weight infants had higher
stimulated estradiol levels, suggesting an increased follicle
complement secreting estradiol either independently or in
response to greater FSH stimulation (16). However, stud-
ies in large groups of women did not demonstrate an in-
creased prevalence of low or high birth weight in women
with PCOS (17, 18), suggesting that it may be an uncom-
mon mechanism. Differences in the intrauterine environ-
ment related to birth order, with contributing factors such
as higher weight in the mother with increased parity, older
maternal age, and placental problems with multiparity,
does not account for the familial difference in the devel-
opment of PCOS among sisters (19).
Caveats exist to the data provided by studies evaluating
the influence of in utero factors on PCOS. In fact, not all
female offspring of women with PCOS will have PCOS.
Only 50% of sisters will manifest PCOS. These sisters
manifest PCOS through hyperandrogenism with irregular
menstrual cycles or hyperandrogenism with regular men-
strual cycles (5). Therefore, the data are diluted by girls
who will likely never go on to develop PCOS. There is also
a high bias of ascertainment when studying only the
daughters of women with PCOS as they may be the most
highly affected or have a more severe form of the disorder.
It is clear that an intrauterine environment that might re-
sult in risk for PCOS also produces girls without PCOS
based on the family data (5).
Puberty and Adolescence
During puberty and adolescence, the signs and symptoms
that characterize PCOS overlap with normal and may re-
quire some time to be established to make a definitive
diagnosis (20). Menstrual irregularities are typical for at
least 2 years after menarche. Irregular menstrual cycles, by
themselves, should therefore not be used as a sole criterion
for the diagnosis of PCOS. Ovarian volume reaches its
maximum at 1.2 to 3.8 years after menarche (21), and
follicle number and volume can exhibit great overlap in
adolescents with PCOS and controls at this time of life
(21). Acne is a common problem in adolescents and is
therefore not a symptom that can be used to identify hy-
perandrogenism. Hirsutism may require several years be-
fore adequate expression. Hyperandrogenemia, as docu-
mented by an elevated androgen level, is the most
persistent and therefore the most useful diagnostic crite-
rion in adolescents (22). Taken together, perhaps the most
reliable diagnostic criteria for PCOS in adolescence is the
presence of all 3 cardinal symptoms of PCOS: hyperan-
drogenemia, irregular menses that persists 2 years after
menarche, and PCO morphology as suggested by in-
creasedovarianvolume.However,areliablediagnosiscan
be made using irregular menses in association with hy-
perandrogenemia if an ultrasound is not available (23).
Premature pubarche, or the development of pubic hair
and axillary hair before age 8 years, may be an early sign
ofPCOS(24).Althoughprematurepubarchemayoccuras
a result of some adrenal androgen disorders (nonclassic
congenital adrenal hyperplasia, androgen-secreting tu-
mors, or Cushing’s syndrome), it can also be due to an
idiopathic early activation of adrenal androgen secretion
from the zona reticularis with production of dehydroepi-
androsterone (DHEA) and DHEA sulfate (DHEAS) in the
⌬5 steroid pathway. Premature adrenarche is not experi-
enced by all girls with PCOS, suggesting that it may ac-
count for one subtype of PCOS (25). On the contrary,
premature adrenarche does not result in PCOS in all cases
(26). Thus, continued monitoring is suggested for girls
given the diagnosis of premature pubarche (26). Persistent
hyperandrogenism remains a distinct feature of girls with
premature pubarche who go on to develop PCOS, and the
hyperandrogenism is exacerbated if a child develops obe-
sity (27).
It is well understood that GnRH pulse frequency is in-
creased in women with PCOS, resulting in high LH levels
and an elevated LH to FSH ratio (28). Increased pulse
frequency of GnRH and an altered diurnal pulse pattern,
occurring even before menarche, is also a prominent fea-
ture in adolescents who develop PCOS (29). The increased
GnRH pulse frequency in adolescents is resistant to sup-
pression by progesterone (30). The increased GnRH pulse
frequency is highly associated with hyperandrogenism
and increased ovarian volume (29). Therefore, the entire
reproductive axis is activated in adolescents with PCOS.
The increased AMH and glucose-stimulated insulin
levelsthatareseenprepubertallyremainelevatedthrough-
out all stages of puberty compared with controls, in the
absence of differences in body mass index (BMI) (9–11,
31, 32). In an analysis of 135 daughters of women with
PCOS and 93 daughters of controls, the daughters of
women with PCOS with the highest AMH also had the
lowest FSH levels, which were expected because a larger
follicle number would be associated with greater secretion
of inhibin B and estradiol. Increased glucose-stimulated
insulin levels are also a consistent phenotype in the daugh-
ters of women with PCOS in mid to late puberty (11, 32).
Thus, higher follicle number, as suggested by AMH levels,
and metabolic features may be an early sign in girls who
may go on to develop PCOS but are not part of the clinical
diagnosis in adolescents.
doi: 10.1210/jc.2013-2375 jcem.endojournals.org 3
5. Based on the relationship between obesity and earlier
menarche, it might be expected that girls who go on to
develop PCOS experience an earlier age at menarche.
However,menarcheingirlswithPCOScanexhibitamuch
wider age range than in control subjects, ranging from
early menarche at or before the age of 9 years to primary
amenorrhea, in which menarche has not yet occurred by
the age of 16 years or 4 years after the onset of thelarche
(33) (Table 2). There is very sparse literature examining
the underlying predictors for age at menarche in PCOS
(19, 33–36). In a retrospective analysis, women with
PCOS were more likely to report early or late menarche
compared with their peers (19). There was also a strong
inverse relationship between reported age and weight at
menarche, suggesting that girls who were overweight had
an earlier menarche, whereas those who were thin com-
pared with their peers experienced a later menarche (19).
Earlier menarche in girls with PCOS might be expected
based on findings that overweight girls experience earlier
pubarche, thelarche, and menarche than those with a nor-
mal BMI (37, 38). The later age at menarche in girls who
report lower weight than their peers during the menar-
cheal window may be related to lower estradiol produc-
tion, although estradiol levels have not been examined in
this group. In addition, the group with later menarche may
have higher androgen levels, as suggested by data from
girls with primary amenorrhea (34, 39). Girls with pri-
mary amenorrhea had higher androgen levels and were
more likely to be overweight (34, 36, 39) or have a family
history of overweight (34), which exacerbates hyperan-
drogenemia. They also had more features of metabolic
syndrome than girls who had an earlier menarche (34, 36,
39). Taken together, overweight may play a greater role in
those with earlier menarche, whereas those presenting
with later menarche may be a mixed group. Lower estra-
diol and/or higher androgen levels exacerbated by obesity
may be distinguishing features in girls with later men-
arche. More work is needed to dissect this group and their
metabolic risk.
Reproductive Years
A recent evidence-based methodology workshop recom-
mended maintaining the broad, inclusionary diagnostic
criteria of Rotterdam for PCOS (40, 41). Using the Rot-
terdam criteria, PCOS can be defined when, in the absence
of another disorder that can cause the same symptoms, 2
of 3 of the following symptoms or signs are present: 1)
irregular menses; 2) hyperandrogenism, either clinical or
biochemical; and/or 3) PCO morphology on pelvic ultra-
sound. Using the Rotterdam criteria, there are 4 possible
diagnostic subcategories of PCOS: 1) irregular menses/
hyperandrogenism/PCO morphology, 2) irregular men-
ses/hyperandrogenism, 3) hyperandrogenism/PCO mor-
phology, and 4) irregular menses/PCO morphology. It is
not clear whether all of these PCOS subsets predispose
women to the same risks for type 2 diabetes and cardio-
vascular risk factors. Several studies have demonstrated
that women with irregular menses/hyperandrogenism/
PCO morphology and irregular menses/hyperandro-
genism have the most severe phenotype and greatest num-
ber of metabolic risk factors. Whether women with
hyperandrogenism/PCO morphology and irregular men-
ses/PCO morphology have the same future cardiovascular
risk has to be determined. Women with irregular menses/
Table 2. Criteria Used to Define Polycystic Ovary Syndrome in Adult Women in Cited Studiesa
Refs.
Defining
Criteria
NIH
Criteria (84)
Rotterdam
Criteria (41) Other
33, 52, 76 Ovarian wedge resection X
71, 46 X X
47, 66 X
48 Oligomenorrhea and normal FSH
49 X X
50 X X
51, 55 X
53, 54 Irregular menses and elevated LH/normal FSH
56 PCO morphology by ultrasound
70, 73 X X
72, 77 Ovarian wedge resection Ovarian dysfunction
80 X
81 X
82 X
83 PCO morphology on ultrasound X
Abbreviation: NIH, National Institutes of Health.
a
Defining criteria were considered the specific feature used to search for PCOS subjects after which other criteria were also required before a
subject was accepted into the study.
4 Welt and Carmina Lifecycle of PCOS J Clin Endocrinol Metab
6. PCO morphology may have the fewest metabolic risk fac-
tors but do have elevated LH levels (42–44). Whether all
of the PCOS subtypes with amenorrhea have similar in-
fertility risk remains to be determined.
The panel also recognized that the incorporated criteria
have limitations, including the fact that the diagnostic fea-
tures of PCOS may change with age (40). The change in
androgens, ovulatory function, and ovarian morphology
with age can complicate the diagnosis of PCOS in adoles-
cents and in older reproductive-age women. PCOS re-
mainsstableonlyduringearlyadultage(18–30years),but
after that time, changes in ovarian and adrenal function
and in metabolic regulation modify the presentation of the
syndrome.
In all women, there is a mild decrease in ovarian an-
drogen secretion of testosterone, particularly in the early
reproductive years between ages 18 and 35 (45). There is
a more marked decrease in adrenal androgen secretion,
including androstenedione and DHEAS, between the ages
of 20 to 25 years and 40 to 45 years (45). Androgen levels
also decline 20% to 30% in women with PCOS. Older
women with PCOS have a lower Ferriman-Gallwey score
and testosterone, androstenedione, and DHEAS levels
compared with younger women, but all values remain
higher than in older control women with the exception of
DHEAS (33, 46–51). Testosterone levels also decrease
when assessed longitudinally and with a more marked
decrease than that in controls, supporting these cross-sec-
tional studies (50, 52).
Ovulatory function also appears to improve with age in
women with PCOS. Menstrual frequency increases (50,
53, 54), with approximately 30% of older women devel-
oping normal ovulatory function (51, 54–56). It has been
suggested that the FSH increase during reproductive aging
may drive follicle development in PCOS (50). Consistent
with this hypothesis, women with PCOS who gain regular
menstrual cyclicity have fewer follicles (53, 54), which
would be expected to result in an increased FSH level. The
return of ovulatory function may also be predicted by a
smaller ovarian volume and lower AMH level, a proxy for
follicle number (55). In one study, all subjects aged 35 to
39 years with AMH levels Յ4 ng/mL at baseline and 60%
of those with AMH levels of Յ5 ng/mL at baseline had
ovulatory function after 5 years (55). When using these
criteria, one must remember that specific AMH levels may
vary with the assay used. Of note, there does not appear to
be a relationship between weight and cycle regularity in
aging (50, 53, 55).
PCO morphology also changes with age (Figure 1).
Data were adapted from a previous study with additional
subjects recruited using the same criteria in the interim and
with identical results (50). Follicle counts in both women
with PCOS and controls decrease with age in a linear fash-
ion (50, 57–60). Importantly, follicle number declines in
a parallel manner with age, although the follicle number is
higher at all ages in women with PCOS compared with
control women during the reproductive years.
Ovarian volume exhibits a log linear decline in women
with PCOS and in controls, but women with PCOS have
a higher initial volume, a lesser slope of decline, and a
greater decrement in the volume change from premeno-
pause to postmenopause (50). A correlation between the
decrease in follicle number and ovarian volume suggests
that the decrease in follicle number may partially explain
the decrease in ovarian volume (57, 61–63). However, the
volume does not decrease as markedly as follicle number
before age 35 years (64), and a lesser decline in the ovarian
A
B
Figure 1. Log ovarian volume (Log Ov Vol) and follicle number (Foll
Num) in women with PCOS and controls (Ctl). A and B, Log ovarian
volume (A) and follicle number (B) in women with PCOS (n ϭ 544; F)
and controls (n ϭ 666; Ⅺ) across reproductive age. Linear regression
was performed for women with PCOS (solid line) and controls (dashed
line). Data include those from a previous publication (50) and
additional subjects recruited using the same criteria in the interim.
Results are the same as previously published (50). The fall in follicle
number is the same in women with PCOS and controls as suggested
by the parallel fall in follicle number, but the number of follicles is
higher in women with PCOS. Ovarian volume is higher in women with
PCOS, and the slope of the line for ovarian volume is less steep than
for controls (P Ͻ .05).
doi: 10.1210/jc.2013-2375 jcem.endojournals.org 5
7. volume despite a similar decline in follicle number in
women with PCOS compared with controls suggests that
a different ovarian compartment, such as the prominent
stromal component (65), accounts for the difference in
slopes (50). Taken together, the decrease in both ovarian
volume and follicle number with age results in loss of
PCO morphology with aging when using the current cri-
teria (41).
A model incorporating the ovarian and androgen
changes with age has also been developed to predict PCOS
at all ages (50). The model includes a combination of age,
follicle number, log ovarian volume, and testosterone: log
(odds of PCOS) ϭ Ϫ10.1302 ϩ 0.0978 ϫ age ϩ 0.2698 ϫ
follicle number ϩ 0.6967 ϫ log volume ϩ 0.0632 ϫ tes-
tosterone. The model predicted PCOS with a receiver op-
erating characteristic curve area of 0.90. A log (odds of
PCOS) score of Ն0.51 results in a specificity of 83% and
a sensitivity of 83% for predicting PCOS.
Late Reproductive Age and Menopause
It is not possible to diagnose a woman with PCOS when
she has already reached menopause because the cardinal
features disappear. Menses cease. Testosterone levels
may no longer be higher than in control women, al-
though less conventional measures of androgen excess
such as the free androgen index and human chorionic
gonadotropin-stimulated androstenedione and 17-hy-
droxyprogesterone levels remain higher (50, 52, 66).
Although it has been suggested that PCO morphology
persists into menopause (56), hypoechoic structures on
ultrasound in postmenopausal women with PCOS cor-
respond to inclusion cysts and vascular structures rather
than follicles, and pathology studies do not demonstrate
secondary follicles in postmenopausal ovaries (50, 67).
Thus, one is able to make the diagnosis of PCOS only
during the reproductive years.
All women experience increasing insulin resistance
and abdominal adiposity along with chronic inflamma-
tion and dyslipidemia with age and a specific increase in
LDL across the menopausal transition (68, 69). It is
therefore possible that the metabolic abnormalities in
women with PCOS also worsen with age. Longitudinal
studies in women with PCOS suggest that waist circum-
ference, cholesterol, and triglyceride levels increase in
women with PCOS as they reach 40 to 50 years (50, 51,
70), whereas BMI increased in some, but not all, studies
(50–52). Fasting insulin and the quantitative insulin
sensitivity check index, ie, metabolic parameters, and
the prevalence of metabolic syndrome did not change
over time in women with PCOS (50, 51). In cross-sec-
tional studies, women with PCOS over the age of 35
years have higher BMI, homeostasis model assessment
(HOMA), glucose, and triglyceride levels compared
with age-matched controls (46, 50, 56, 71, 72). A large
longitudinal study of women with PCOS demonstrated
a prevalence of type 2 diabetes of 39%, exceeding the
prevalence of 5.8% in the general population (73).
However, the high prevalence of type 2 diabetes is likely
related to the very high BMI in those women (73), be-
cause other studies do not demonstrate an increase in
diabetes prevalence in this age group (74). Consistently,
cross-sectional studies of menopausal women with
PCOS compared with menopausal controls demon-
strate that only the insulin area under the curve re-
mained significantly higher in women with PCOS when
controlled for the higher BMI (66).
There may be a subset of women with PCOS who
actually have an improvement in cardiovascular risk
with age. In a longitudinal study, the occurrence of ovu-
latory function with aging in women with PCOS was
inversely correlated with changes in LDL-cholesterol.
In contrast, women who remained anovulatory had in-
creases in total cholesterol, LDL-cholesterol, and non–
high-density lipoprotein-cholesterol levels and cardio-
vascular risk remained significantly higher than in the
general population (51). In contrast, an earlier onset of
irregular menses does not appear to be associated with
a more severe metabolic phenotype than in women with
a later onset of irregular menses (75). The underlying
cause of the factor resulting in improvement in ovula-
tory cycles and cardiovascular risk with age needs to be
determined.
There are few studies in which both women with
PCOS and controls are followed longitudinally from
early reproductive age into menopause. In the available
studies, it is interesting to note that weight and systolic
blood pressure increase with increasing age in controls,
whereas women with PCOS had little to no increase so
that there was no difference in these parameters in
women with PCOS and controls at the older age (50, 52,
76) (Table 1). Similarly, the waist to hip ratio in the
control group matched that of the PCOS group at the
older age because of the weight gain in the control group
(50, 52, 76). Although there was an increased preva-
lence of type 2 diabetes in women with PCOS compared
with controls at a younger age, the prevalence of type 2
diabetes increased with age in controls, and there was
no difference in the prevalence of diabetes 20 years later
when women with PCOS had reached menopause (52,
76). There was also no difference in fasting insulin lev-
els, HOMA of insulin resistance, and glucose levels in
the two groups at an older age (52). However, the prev-
6 Welt and Carmina Lifecycle of PCOS J Clin Endocrinol Metab
8. alence of hypertension was higher in postmenopausal
women with PCOS compared with controls studied lon-
gitudinally, and triglyceride levels increased in both
groups but remained higher in the women with PCOS
(52, 76, 77). Thus, longitudinal data provide evidence
that control women tend to have worsening of some of
their metabolic parameters to a range seen in the PCOS
subjects over time, whereas women with PCOS have
more components of the metabolic syndrome starting at
an early age and therefore have a longer exposure to
these adverse cardiovascular risk factors.
Despite the longer exposure to these cardiovascular
risk factors, it is difficult to demonstrate an increased
risk of morbidity and mortality in women with PCOS.
There has been only one small longitudinal study and
one retrospective cohort study in women diagnosed
with PCOS in their reproductive years and controls to
assess risk of mortality and cardiovascular morbidity
into menopause, up to age 70 years (76, 77). These
studies have not demonstrated an increased risk of myo-
cardial infarction or death from cardiovascular disease
or increased total mortality from any cause in women
with PCOS (76). Only the retrospective cohort study
demonstrated an increased risk of stroke (77), but the
group also had a higher BMI, more diabetes, and more
cardiovascular risk factors overall. Taken together, ad-
ditional studies are needed to determine whether the
increased cardiovascular risk in reproductive life trans-
lates into an increased cardiovascular morbidity and
mortality in later life for women with PCOS. However,
it is possible that in most women with PCOS the car-
diovascular risk normalizes with age, whereas in a sub-
group, perhaps in the patients maintaining high andro-
gen levels also after menopause, the cardiovascular risk
remains increased and affects the morbidity. Only lon-
gitudinal studies in large populations of women with
PCOS will answer this question.
When diseases are common, it is possible that some
aspect of what is now disease gave humans a selective
advantage in a different environment. For example, the
thrifty gene hypothesis proposes that positive selection of
metabolic traits that were advantageous in times of star-
vation, allowing efficient use of fuels and prevention of
weight loss, are disadvantageous in the modern world
where food is plentiful (78). These genetic changes may
now result in an increased risk of type 2 diabetes (78).
Similarly, women with PCOS may have a selective advan-
tage in the population based on a longer reproductive lifes-
pan, but menstrual cycles may become irregular with the
weight gain that is common in modern society. The longer
reproductivelifespaninwomenwithPCOSissuggestedby
the greater number of follicles and the attenuated fall in
ovarian volume across reproductive aging in both cross-
sectional and longitudinal studies (50). Similarly, AMH
levels, a marker of antral follicle number (79, 80), exhibit
a less pronounced longitudinal decrease across aging in
women with PCOS (81), resulting in an estimated meno-
pausal age 2 years later than in controls (82). Although the
irregular menstrual cyclicity in women with PCOS might
be expected to decrease fertility, one longitudinal study
suggested that there was no difference in pregnancy rates
for the first child and that a majority of women with PCOS
had achieved a spontaneous pregnancy (83). Despite the
promising signs of a longer reproductive lifespan, longi-
tudinal and retrospective studies have yet to document a
later age at menopause (52, 77). Taken together, the data
suggest that ovarian aging in women with PCOS is delayed
compared with that in control women, but further longi-
tudinal evidence is also needed.
Summary
ItisclearthatthephenotypeinwomenwithPCOSchanges
across the lifespan. It will be straightforward to create
age-based criteria to diagnose PCOS during the reproduc-
tive years given the wealth of data. Following women with
PCOS into menopause will help define the true cardiovas-
cular morbidity and mortality. Finally, with our increas-
ing understanding of the environmental factors and genes
that predispose to PCOS, we may soon be able to fully
elucidate the phenotype in prepubertal girls in an unbiased
fashion. These ongoing studies will provide a thorough
understanding of the PCOS lifecycle, to help with diag-
nosis and treatment that is no longer limited to the repro-
ductive-age patient.
Acknowledgments
Address all correspondence and requests for reprints to: Corrine
K. Welt, Reproductive Endocrine, BHX 511, Massachusetts
General Hospital, 55 Fruit Street, Boston, Massachusetts 02114.
E-mail: cwelt@partners.org.
This work was supported by the National Institutes of Health
1R01HD065029 (to C.K.W.), ADA 1-10-CT-57 (to C.K.W.),
and 1 UL1 RR025758 to Harvard Clinical and Translational
Science Center.
Disclosure Summary: The authors have nothing to disclose.
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